Polycystic kidney disease 12 gene and uses thereof

A diagnostic kit for amplifying a mutant PKD1 gene, comprising a pair of nucleic acid primers complementary to the PKD1 nucleic acid sequence according to Seq. I.D. No.:

• 7, wherein said mutant PKD1 gene comprises a nucleic acid sequence wherein a sequence selected from the group consisting of the following ((a)-(l)) is deleted:
• (a) (OX114) a nucleic acid comprising 446 base pairs between nucleotides 1746-2192 as defined in Seq. I.D. No. 1;
• (b) (OX32) a nucleic acid comprising 135 base pairs between nucleotides 3696-3831 as defined in Seq. I.D. No. 1;
• (c) (OX875) a nucleic acid comprising about 5.5 Kb flanked by the two Xbal sites shown in FIG. 3a and encompassing the EcoR1 site separating the CW10 (41 kb) and JH1 (18 kb) fragment;
• (d) (WS-53) a nucleic acid comprising about 100 kb encompassing the PKD1 gene, wherein the 3′ end of said nucleic acid lies between the JH1 and CW21 fragment and the 5′ end of said nucleic acid lies between the SM6 and JH17 fragment shown in FIG. 6;
• (e) (WS-215) a nucleic acid comprising about 160 kb encompassing the PKD1 gene, wherein said nucleic acid extends 3′ of the PKD1 gene to within fragment CW15 and 5′ of the PKD1 gene to between fragments SM6 and JH17 as shown in FIG. 12;
• (f) (WS-227) a nucleic acid comprising about 50 kb encompassing the PKD1 gene, wherein said nucleic acid extends 3′ of the PKD1 gene to within fragment CW20 and 5′ of the PKD1 gene to within fragment JH11 as shown in FIG. 12;
• (g) (WS-219) a nucleic acid comprising about 27 kb encompassing a portion of the PKD1 gene, wherein said nucleic acid extends 3′ of the PKD1 gene within fragment JH1 and into the PKD1 gene to within fragment JH6 as shown in FIG. 12;
• (h) (WS-250) a nucleic acid comprising about 160 kb encompassing the PKD1 gene, wherein said nucleic acid extends 3′ of the PKD1 gene to within fragment CW20 and 5′ of the PKD1 gene to within fragment BLu24 as shown in FIGS. 1a and 12:
• (i) (WS-194) a nucleic acid comprising about 65 kb encompassing the PKD1 gene, wherein said nucleic acid extends 3′ of the PKD1 gene to within fragment CW20 and 5′ of the PKD1 gene to within fragment CW10;
• (j) (461) a nucleic acid comprising 18 base pairs in the 75 base pair intron amplified by the primer pair 3A3C (Seq. I.D. No.s:
• 11 and 12) insert at position 3696 of the 3′ sequence as shown in FIG. 11;
• (k) (OX1054) a nucleic acid comprising 20 base pairs in the 75 base pair intron amplified by the primer pair 3A3C (Seq. I.D. Nos.:
• 11 and 12) insert at position 3696 of the 3′ sequence as shown in FIG. 11;
• and
• (l) (WS-212) a nucleic acid comprising about 75 kb located downstream of the PKD1 gene and located between fragments SM9 and CW9 distal of the PKD1 gene and the PKD1 3′UTR proximal to the PKD1 gene as shown in FIG. 12.

A diagnostic kit for carrying out a method for determining whether said subject is a PKD1-associated disorder carrier or a patient having a PKD1-associated disorder, which method comprises detecting the presence or absence of PKD1 nucleic acid in a biological sample from a subject, wherein detection of a mutant PKD1 nucleic acid or the absence of a PKD1 nucleic acid is indicative of a genetic mutation giving rise to a PKD1-associated disorder, wherein said mutant PKD1 comprises a nucleic acid wherein a sequence selected from the group consisting of the following ((a)-(l)) is deleted:

• (a) (OX114) a nucleic acid comprising 446 base pairs between nucleotides 1746-2192 as defined in Seq. I.D. No. 1;
• (b) (OX32) a nucleic acid comprising 135 base pairs between nucleotides 3696-3831 as defined in Seq. I.D. No. 1;
• (c) (OX875) a nucleic acid comprising about 5.5 Kb flanked by the two Xbal sites shown in FIG. 3a and encompassing the EcoR1 site separating the CW10 (41 kb) and JH1 (18 kb) fragment;
• (d) (WS-53) a nucleic acid comprising about 100 kb encompassing the PKD1 gene, wherein the 3′ end of said nucleic acid lies between the JH1 and CW21 fragment and the 5′ end of said nucleic acid lies between the SM6 and JH17 fragment shown in FIG. 6;
• (e) (WS-215) a nucleic acid comprising about 160 kb encompassing the PKD1 gene, wherein said nucleic acid extends 3′ of the PKD1 gene to within fragment CW15 and 5′ of the PKD1 gene to between fragments SM6 and JH17 as shown in FIG. 12;
• (f) (WS-227) a nucleic acid comprising about 50 kb encompassing the PKD1 gene, wherein said nucleic acid extends 3′ of the PKD1 gene to within fragment CW20 and 5′ of the PKD1 gene to within fragment JH11 as shown in FIG. 12;
• (g) (WS-219) a nucleic acid comprising about 27 kb encompassing a portion of the PKD1 gene, wherein said nucleic acid extends 3′ of the PKD1 gene within fragment JH1 and into the PKD1 gene to within fragment JH6 as shown in FIG. 12;
• (h) (WS-250) a nucleic acid comprising about 160 kb encompassing the PKD1 gene, wherein said nucleic acid extends 3′ of the PKD1 gene to within fragment CW20 and 5′ of the PKD1 gene to within fragment BLu24 as shown in FIGS. 1a and 12:
• (i) (WS-194) a nucleic acid comprising about 65 kb encompassing the PKD1 gene, wherein said nucleic acid extends 3′ of the PKD1 gene to within fragment CW20 and 5′ of the PKD1 gene to within fragment CW10;
• (j) (461) a nucleic acid comprising 18 base pairs in the 75 base pair intron amplified by the primer pair 3A3C (Seq. I.D. No.s:
• 11 and 12) insert at position 3696 of the 3′ sequence as shown in FIG. 11;
• (k) (OX1054) a nucleic acid comprising 20 base pairs in the 75 base pair intron amplified by the primer pair 3A3C (Seq. I.D. No.s:
• 11 and 12) insert at position 3696 of the 3′ sequence as shown in FIG. 11;
• and
• (l) (WS-212) a nucleic acid comprising about 75 kb located downstream of the PKD1 gene and located between fragments SM9 and CW9 distal of the PKD1 gene and the PKD1 3′UTR proximal to the PKD1 gene as shown in FIG. 12, and
• which kit includes a nucleic acid probe capable of hybridizing to a sequence according to Seq. I.D. No. 7, wherein said probe is selected from the group consisting of 8S3, 8S1, 1A1H.6, AH3, CW10, JH17, JH5, JH6, JH8, JH4, JH13 , HG-4/1.1, CE18, Blu24, H2, gap α 22, gap gamma, S1-S3, SM3, JH12, JH10, DFS5, JH14, SM9, CW9, CW15, CW18, CW20, JH11, CW36, JH14, A1C, 461, OX1054, B1E, 21p.9, 1A-7, AH6, BFS5 and JH9.

A diagnostic kit for carrying out a method for determining whether said subject is a PKD1-associated disorder carrier or a patient having a PKD1-associated disorder, which kit includes a nucleic acid probe capable of detecting an isolated mutant PKD1 nucleic acid and;

• wherein said nucleic acid probe is an RNA transcript comprising a sequence complementary to the coding region of the nucleic acid sequence as presented in Seq. I.D. No. 7 or the complementary strand and comprising a length of about 14 kB, and wherein said mutant PKD1 nucleic acid comprises a nucleic acid sequence wherein a sequence selected from the group consisting of the following ((a)-(l)) is deleted:
• (a) (OX114) a nucleic acid comprising 446 base pairs between nucleotides 1746-2192 as defined in Seq. I.D. No. 1;
• (b) (OX32) a nucleic acid comprising 135 base pairs between nucleotides 3696-3831 as defined in Seq. I.D. No. 1;
• (c) (OX875) a nucleic acid comprising about 5.5 Kb flanked by the two Xbal sites shown in FIG. 3a and encompassing the EcoR1 site separating the CW10 (41 kb) and JH1 (18 kb) fragment;
• (d) (WS-53) a nucleic acid comprising about 100 kb encompassing the PKD1 gene, wherein the 3′ end of said nucleic acid lies between the JH11 and CW21 fragment and the 5′ end of said nucleic acid lies between the SM6 and JH17 fragment shown in FIG. 6;
• (e) (WS-215) a nucleic acid comprising about 160 kb encompassing the PKD1 gene, wherein said nucleic acid extends 3′ of the PKD1 gene to within fragment CW15 and 5′ of the PKD1 gene to between fragments SM6 and JH17 as shown in FIG. 12;
• (f) (WS-227) a nucleic acid comprising about 50 kb encompassing the PKD1 gene, wherein said nucleic acid extends 3′ of the PKD1 gene to within fragment CW20 and 5′ of the PKD1 gene to within fragment JH11 as shown in FIG. 12;
• (g) (WS-219) a nucleic acid comprising about 27 kb encompassing a portion of the PKD1 gene, wherein said nucleic acid extends 3′ of the PKD1 gene within fragment JH1 and into the PKD1 gene to within fragment JH6 as shown in FIG. 12;
• (h) (WS-250) a nucleic acid comprising about 160 kb encompassing the PKD1 gene, wherein said nucleic acid extends 3′ of the PKD1 gene to within fragment CW20 and 5′ of the PKD1 gene to within fragment BLu24 as shown in FIGS. 1a and 12:
• (i) (WS-194) a nucleic acid comprising about 65 kb encompassing the PKD1 gene, wherein said nucleic acid extends 3′ of the PKD1 gene to within fragment CW20 and 5′ of the PKD1 gene to within fragment CW10;
• (j) (461) a nucleic acid comprising 18 base pairs in the 75 base pair intron amplified by the primer pair 3A3C (Seq. I.D. No.s:
• 11 and 12) insert at position 3696 of the 3′ sequence as shown in FIG. 11;
• (k) (OX1054) a nucleic acid comprising 20 base pairs in the 75 base pair intron amplified by the primer pair 3A3C (Seq. I.D. No.s:
• 11 and 12) insert at position 3696 of the 3′ sequence as shown in FIG. 11;
• and
• (l) (WS-212) a nucleic acid comprising about 75 kb located downstream of the PKD1 gene and located between fragments SM9 and CW9 distal of the PKD1 gene and the PKD1 3′UTR proximal to the PKD1 gene as shown in FIG. 12.

A diagnostic kit for detecting a mutant PKD1 nucleic acid, wherein said mutant PKD1 nucleic acid comprises a nucleic acid sequence wherein a sequence selected from the group consisting of the following ((a)-(l)) is deleted:

• (a) (OX114) a nucleic acid comprising 446 base pairs between nucleotides 1746-2192 as defined in Seq. I.D. No. 1;
• (b) (OX32) a nucleic acid comprising 135 base pairs between nucleotides 3696-3831 as defined in Seq. I.D. No. 1;
• (c) (OX875) a nucleic acid comprising about 5.5 Kb flanked by the two Xbal sites shown in FIG. 3a and encompassing the EcoR1 site separating the CW10 (41 kb) and JH1 (18 kb) fragment;
• (d) (WS-53) a nucleic acid comprising about 100 kb encompassing the PKDD1 gene, wherein the 3′ end of said nucleic acid lies between the JH1 and CW21 fragment and the 5′ end of said nucleic acid lies between the SM6 and JH17 fragment shown in FIG. 6;
• (e) (WS-215) a nucleic acid comprising about 160 kb encompassing the PKD1 gene, wherein said nucleic acid extends 3′ of the PKD1 gene to within fragment CW15 and 5′ of the PKD1 gene to between fragments SM6 and JH17 as shown in FIG. 12;
• (f) (WS-227) a nucleic acid comprising about 50 kb encompassing the PKD1 gene, wherein said nucleic acid extends 3′ of the PKD1 gene to within fragment CW20 and 5′ of the PKD1 gene to within fragment JH11 as shown in FIG. 12;
• (g) (WS-219) a nucleic acid comprising about 27 kb encompassing a portion of the PKD1 gene, wherein said nucleic acid extends 3′ of the PKD1 gene within fragment JH1 and into the PKD1 gene to within fragment JH6 as shown in FIG. 12;
• (h) (WS-250) a nucleic acid comprising about 160 kb encompassing the PKD1 gene, wherein said nucleic acid extends 3′ of the PKD1 gene to within fragment CW20 and 5′ of the PKD1 gene to within fragment BLu24 as shown in FIGS. 1a and 12:
• (i) (WS-194) a nucleic acid comprising about 65 kb encompassing the PKD1 gene, wherein said nucleic acid extends 3′ of the PKD1 gene to within fragment CW20 and 5′ of the PKD1 gene to within fragment CW10;
• (j) (461) a nucleic acid comprising 18 base pairs in the 75 base pair intron amplified by the primer pair 3A3C (Seq. I.D. No.s:
• 11 and 12) insert at position 3696 of the 3′ sequence as shown in FIG. 11;
• (k) (OX1054) a nucleic acid comprising 20 base pairs in the 75 base pair intron amplified by the primer pair 3A3C (Seq. I.D. No.s:
• 11 and 12) insert at position 3696 of the 3′ sequence as shown in FIG. 11;
• and
• (l) (WS-212) a nucleic acid comprising about 75 kb located downstream of the PKD1 gene and located between fragments SM9 and CW9 distal of the PKD1 gene and the PKD1 3′UTR proximal to the PKD1 gene as shown in FIG. 12, and
• wherein said kit includes the DNA probe CW10 (Seq. I.D. No. 4).

A diagnostic kit for detecting a mutant PKD1 nucleic acid, wherein said mutant PKD1 nucleic acid comprises a nucleic acid sequence wherein a sequence selected from the group consisting of the following ((a)-(l)) is deleted:

• (a) (OX114) a nucleic acid comprising 446 base pairs between nucleotides 1746-2192 as defined in Seq. I.D. No. 1;
• (b) (OX32) a nucleic acid comprising 135 base pairs between nucleotides 3696-3831 as defined in Seq. I.D. No. 1;
• (c) (OX875) a nucleic acid comprising about 5.5 Kb flanked by the two Xbal sites shown in FIG. 3a and encompassing the EcoR1 site separating the CW10 (41 kb) and JH1 (18 kb) fragment;
• (d) (WS-53) a nucleic acid comprising about 100 kb encompassing the PKD1 gene, wherein the 3′ end of said nucleic acid lies between the JH1 and CW21 fragment and the 5′ end of said nucleic acid lies between the SM6 and JH17 fragment shown in FIG. 6;
• (e) (WS-215) a nucleic acid comprising about 160 kb encompassing the PKD1 gene, wherein said nucleic acid extends 3′ of the PKD1 gene to within fragment CW15 and 5′ of the PKD1 gene to between fragments SM6 and JH17 as shown in FIG. 12;
• (f) (WS-227) a nucleic acid comprising about 50 kb encompassing the PKD1 gene, wherein said nucleic acid extends 3′ of the PKD1 gene to within fragment CW20 and 5′ of the PKD1 gene to within fragment JH11 as shown in FIG. 12;
• (g) (WS-219) a nucleic acid comprising about 27 kb encompassing a portion of the PKD1 gene, wherein said nucleic acid extends 3′ of the PKD1 gene within fragment JH1 and into the PKD1 gene to within fragment JH6 as shown in FIG. 12;
• (h) (WS-250) a nucleic acid comprising about 160 kb encompassing the PKD1 gene, wherein said nucleic acid extends 3′ of the PKD1 gene to within fragment CW20 and 5′ of the PKD1 gene to within fragment BLu24 as shown in FIGS. 1a and 12:
• (i) (WS-194) a nucleic acid comprising about 65 kb encompassing the PKD1 gene, wherein said nucleic acid extends 3′ of the PKD1 gene to within fragment CW20 and 5′ of the PKD1 gene to within fragment CW10;
• (j) (461) a nucleic acid comprising 18 base pairs in the 75 base pair intron amplified by the primer pair 3A3C (Seq. I.D. No.s:
• 11 and 12) insert at position 3696 of the 3′ sequence as shown in FIG. 1;
• (k) (OX1054) a nucleic acid comprising 20 base pairs in the 75 base pair intron amplified by the primer pair 3A3C (Seq. I.D. No.s:
• 11 and 12) insert at position 3696 of the 3′ sequence as shown in FIG. 11;
• and
• (l) (WS-212) a nucleic acid comprising about 75 kb located downstream of the PKD1 gene and located between fragments SM9 and CW9 distal of the PKD1 gene and the PKD1 3′UTR proximal to the PKD1 gene as shown in FIG. 12, and
• wherein said kit includes the DNA probe 1A1H.6 (Seq. I.D. No. 3).

A diagnostic kit for carrying out a method for determining whether said subject is a PKD1 associated disorder carrier or a patient having a PKD1-associated disorder, which kit includes a nucleic acid probe capable of detecting a nucleic acid sequence wherein a sequence selected from the group consisting of the following ((a)-(l)) is deleted:

• (a) (OX114) a nucleic acid comprising 446 base pairs between nucleotides 1746-2192 as defined in Seq. I.D. No. 1;
• (b) (OX32) a nucleic acid comprising 135 base pairs between nucleotides 3696-3831 as defined in Seq. I.D. No. 1;
• (c) (OX875) a nucleic acid comprising about 5.5 Kb flanked by the two Xbal sites shown in FIG. 3a and encompassing the EcoR1 site separating the CW10 (41 kb) and JH1 (18 kb) fragment;
• (d) (WS-53) a nucleic acid comprising about 100 kb encompassing the PKD1 gene, wherein the 3′ end of said nucleic acid lies between the JH1 and CW21 fragment and the 5′ end of said nucleic acid lies between the SM6 and JH17 fragment shown in FIG. 6;
• (e) (WS-215) a nucleic acid comprising about 160 kb encompassing the PKD1 gene, wherein said nucleic acid extends 3′ of the PKD1 gene to within fragment CW15 and 5′ of the PKD1 gene to between fragments SM6 and JH17 as shown in FIG. 12;
• (f) (WS-227) a nucleic acid comprising about 50 kb encompassing the PKD1 gene, wherein said nucleic acid extends 3′ of the PKD1 gene to within fragment CW20 and 5′ of the PKD1 gene to within fragment JH11 as shown in FIG. 12;
• (g) (WS-219) a nucleic acid comprising about 27 kb encompassing a portion of the PKD1 gene, wherein said nucleic acid extends 3′ of the PKD1 gene within fragment JH1 and into the PKD1 gene to within fragment JH6 as shown in FIG. 12;
• (h) (WS-250) a nucleic acid comprising about 160 kb encompassing the PKD1 gene, wherein said nucleic acid extends 3′ of the PKD1 gene to within fragment CW20 and 5′ of the PKD1 gene to within fragment BLu24 as shown in FIGS. 1a and 12:
• (i) (WS-194) a nucleic acid comprising about 65 kb encompassing the PKD1 gene, wherein said nucleic acid extends 3′ of the PKD1 gene to within fragment CW20 and 5′ of the PKD1 gene to within fragment CW10;
• (j) (461) a nucleic acid comprising 18 base pairs in the 75 base pair intron amplified by the primer pair 3A3C (Seq. I.D. No.s:
• 11 and 12) insert at position 3696 of the 3′ sequence as shown in FIG. 11;
• (k) (OX1054) a nucleic acid comprising 20 base pairs in the 75 base pair intron amplified by the primer pair 3A3C (Seq. I.D. No.s:
• 11 and 12) insert at position 3696 of the 3′ sequence as shown in FIG. 11;
• and
• (l) (WS-212) a nucleic acid comprising about 75 kb located downstream of the PKD1 gene and located between fragments SM9 and CW9 distal of the PKD1 gene and the PKD1 3′UTR proximal to the PKD1 gene as shown in FIG. 12,
• and wherein said probe is selected from the group consisting of 8S3, 8S1, 1A1H.6, AH3, CW10, JH17, JH5, JH6, JH8, JH4, JH13, HG-4/1.1, CE18, Blu24, H2, gap α 22, gap gamma, S1-S3, SM3, JH12, JH10, DFS5, JH14, SM9, CW9, CW15, CW18, CW20, JH11, CW36, JH14, A1C, 461, OX1054, B1E, 21p.9, 1A-7, AH6, BFS5 and JH9.